Improved understanding of the pathogenesis of dementia brings renewed hope that scientists might soon discover disease-modifying treatments for this debilitating disorder. Initial evidence suggests that disease-modifying treatments would be the most effective if clinicians employed them early, in the preclinical phase. Disease-modifying treatments for dementia are likely to have potentially serious side effects or complications, and therefore it will be vital to identify patients as early and accurately as possible. The term cognitive impairment-no dementia (CIND) has been used to describe this preclinical state. CIND captures a broad range of pathways to dysfunction and the course of this condition is variable with some subjects remaining stable for long period while other convert to dementia and other revert to apparent normalcy. In this proposal, we seek to examine the role of cardiovascular risk factors on diagnosed cognitive status cross-sectionally and longitudinally. We propose to do this in the primary care environment where wide-scale treatment of these patients will occur. A random sample of 2000 patients aged 65 and older from the Wishard Health System primary care database will be evaluated and diagnosed. Patients with CIND will be followed (and re-diagnosed) annually for 4 years. Thorough procedures for assessment will assure optimum diagnostic accuracy. The extensive Regenstrief Medical Records System will allow retrospective and prospective capture of a wide range of health and medical information and the mapping of this information onto clinical diagnosis over time. In this way, we will be able to improve our understanding of which older adults with cognitive impairment-no dementia (CIND) will progress to dementia and would thus be the most likely to benefit from early initiation of disease-modifying treatments. [unreadable] [unreadable] [unreadable]